BAK会改变神经元兴奋性，并且在出生后发育过程中能够从抗死亡功能转变为促死亡功能。

BAK alters neuronal excitability and can switch from anti- to pro-death function during postnatal development.

作者信息

Fannjiang Yihru, Kim Chong-Hyun, Huganir Richard L, Zou Shifa, Lindsten Tullia, Thompson Craig B, Mito Toshiaki, Traystman Richard J, Larsen Thomas, Griffin Diane E, Mandir Allen S, Dawson Ted M, Dike Sonny, Sappington Andrea L, Kerr Douglas A, Jonas Elizabeth A, Kaczmarek Leonard K, Hardwick J Marie

机构信息

Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

出版信息

Dev Cell. 2003 Apr;4(4):575-85. doi: 10.1016/s1534-5807(03)00091-1.

DOI:10.1016/s1534-5807(03)00091-1

PMID:12689595

Abstract

BAK is a pro-apoptotic BCL-2 family protein that localizes to mitochondria. Here we evaluate the function of BAK in several mouse models of neuronal injury including neuronotropic Sindbis virus infection, Parkinson's disease, ischemia/stroke, and seizure. BAK promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. BAK protects neurons from excitotoxicity and virus infection in the hippocampus. As mice mature, BAK is converted from anti- to pro-death function in virus-infected spinal cord neurons. In addition to regulating cell death, BAK also protects mice from kainate-induced seizures, suggesting a possible role in regulating synaptic activity. BAK can alter neurotransmitter release in a direction consistent with its protective effects on neurons and mice. These findings suggest that BAK inhibits cell death by modifying neuronal excitability.

摘要

BAK是一种定位于线粒体的促凋亡BCL-2家族蛋白。在此，我们在几种神经元损伤的小鼠模型中评估BAK的功能，这些模型包括嗜神经性辛德毕斯病毒感染、帕金森病、缺血/中风和癫痫发作。根据特定的死亡刺激、神经元亚型和出生后发育阶段，BAK可促进或抑制神经元死亡。BAK保护海马体中的神经元免受兴奋性毒性和病毒感染。随着小鼠成熟，BAK在病毒感染的脊髓神经元中从抗死亡功能转变为促死亡功能。除了调节细胞死亡外，BAK还保护小鼠免受海藻酸诱导的癫痫发作，提示其在调节突触活动中可能发挥作用。BAK可改变神经递质释放，其方向与其对神经元和小鼠的保护作用一致。这些发现表明，BAK通过改变神经元兴奋性来抑制细胞死亡。